EMB ‐01, a Tetravalent Bispecific Antibody, Inducing Co‐Degradation of EGFR and c‐Met for Enhanced Anti‐Tumor Efficacy

The bispecific antibody EMB‐01 (bafisontamab), constructed using EpimAb's proprietary FIT‐Ig platform, is designed to simultaneously target epidermal growth factor receptor (EGFR) and receptor tyrosine kinase Met (c‐Met). Here, we characterize EMB‐01's binding properties, mechanisms of action, and anti‐tumor efficacy using in vitro cell line models and in vivo models (patient‐derived xenografts, PDXs). EMB‐01 exhibits high‐affinity binding to EGFR and c‐Met, induces co‐degradation of both receptors, enhances endocytosis, and elicits strong antibody‐dependent cellular cytotoxicity (ADCC) and complement‐dependent cytotoxicity (CDC) effects. Mechanistically, EMB‐01 effectively inhibits ligand‐induced receptor phosphorylation, downstream AKT activation, and IL‐8 secretion. Furthermore, EMB‐01 demonstrates potent anti‐tumor activity across multiple tumor models, outperforming existing EGFR‐targeted therapies and other bispecific antibodies, while maintaining favorable pharmacokinetics with good tolerability in cynomolgus monkeys. These findings support the clinical development of EMB‐01 as a promising therapeutic for EGFR/c‐Met–driven cancers.